Mechanism by which Quinarpril improves vascular function in coronary artery disease

Angiotensin-converting enzyme (ACE) inhibition has been shown to improve en dothelium-dependent vasodilator responsiveness, but the contribution and me chanism of enhanced nitric oxide (NO) bioactivity to this effect in patient s with coronary artery disease are unknown. We investigated the effect of A CE inhibition on brachial artery dilator responsiveness to increased shear stress after forearm ischemia by ultrasonography asa bioassay for endotheli al NO available to vascular smooth muscle in 9 men with coronary artery dis ease, Serum nitrogen oxides were measured after 3 days of nitrate-restricte d diet as an index of endothelial NO release. Patients received quinapril 2 0 to 40 mg/day for 8 weeks. Relative to pretreatment measurements, quinapri l increased flow-mediated dilation (from 2.4 +/- 0.4 to 10.8 +/- 2.2, p < 0 .001), with significant improvement persisting 1 week after discontinuation of therapy (6.7 +/- 2.5%, p < 0.01). However, quinapril decreased serum ni trogen oxide levels by 19 +/- 17% compared with pretreatment values (from 5 8.2 +/- 19.0 to 46.0 +/- 13.3 mu mol/L, p < 0.01). Thus, ACE inhibitor ther apy with quinapril selectively improves endothelium-dependent vasodilator r esponsiveness by increased NO bioactivity in relation to vascular smooth mu scle in patients with coronary artery disease, an effect achieved at a lowe r rate of NO release from the endothelium. These findings suggest that ACE inhibitors may reduce angiotensin Ii-induced oxidant stress within the vess el wall and protect NO from oxidative inactivation. This effect may reduce endothelial NO synthesis required for vasomotor regulation. (C)1999 by Exce rpta Medica, Inc.